# US 11,897,941 B2 · Compositions and methods for reducing bacterial aggregation

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- Number: US 11,897,941 B2
- Document ID: US11897941B2
- Status: Granted
- Kind: B2
- Application number: 17/181,491
- Filed: 2021-02-22
- Published: 2021-09-23
- Granted: 2024-02-13
- Earliest claimed: 2018-08-23
- Assignees: La Trobe University; The University of Queensland
- Applicants: La Trobe University; The University of Queensland
- Inventors: Begona Heras; Jason Paxman; Mark Schembri; Alvin Lo
- Web page: https://patentgrep.com/patent/US11897941B2

## CPC

- C07K 16/1232: Escherichia (G)
- A01N 63/50: Isolated enzymes; Isolated proteins (peptides A01N37/46)
- A61K 39/40: bacterial
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/04: Antibacterial agents
- C07K 14/245: Escherichia (G)
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to compositions and methods for inhibiting bacterial aggregation, and in particular, to compositions and methods that inhibit autotransporter-mediated bacterial aggregation or attachment. Described herein are autotransporter binding molecules such as antibodies and antigen binding fragments thereof. The autotransporter binding molecules block self-association between autotransporters and autotransporter-mediated surface attachment.

## Claims

### Claim 1

An isolated antibody or antigen binding fragment thereof comprising:
a) a CDRH1 comprising the sequence set forth in SEQ ID NO: 3;
a CDRH2 comprising the sequence set forth in SEQ ID NO: 4;
a CDRH3 comprising the sequence set forth in SEQ ID NO: 5;
a CDRL1 comprising the sequence set forth in SEQ ID NO: 6;
a CDRL2 comprising the sequence set forth in SEQ ID NO: 7; and
a CDRL3 comprising the sequence set forth in SEQ ID NO: 8; or
b) a CDRH1 comprising the sequence set forth in SEQ ID NO: 15;
a CDRH2 comprising the sequence set forth in SEQ ID NO: 16;
a CDRH3 comprising the sequence set forth in SEQ ID NO: 17;
a CDRL1 comprising the sequence set forth in SEQ ID NO: 18;
a CDRL2 comprising the sequence set forth in SEQ ID NO: 19; and
a CDRL3 comprising the sequence set forth in SEQ ID NO: 20.

### Claim 2 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, further comprising:
a) a heavy chain variable region (VH) comprising the sequence set forth in SEQ ID NO: 9 or a sequence having at least 90% identity to SEQ ID NO: 9, and a light chain variable region (VL) comprising the sequence set forth in SEQ ID NO: 10 or a sequence having at least 90% identity to SEQ ID NO: 10; or
b) a VH comprising the sequence set forth in SEQ ID NO: 21 or a sequence having at least 90% identity to SEQ ID NO: 21, and a VL comprising the sequence set forth in SEQ ID NO: 22 or a sequence having at least 90% identity to SEQ ID NO: 22.

### Claim 3 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment binds to Ag43a (SEQ ID NO: 1) at an epitope comprising one or more residues selected from the group consisting of N83, R113, N114, D133, N150, T151, T152, G169, R254, E270, T291, T310, R330, G332, A333, 5335, T361, N362, R364, T380, T381, S383, N386, S399, T401, D404 and G405.

### Claim 4 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment a) specifically binds to an autotransporter or b) reduces binding of one autotransporter molecule to another autotransporter molecule.

### Claim 5 (depends on 1)

An isolated nucleic acid encoding a) the antibody or antigen binding fragment thereof of claim 1 or b) the VH or the VL of the antibody or antigen binding fragment thereof.

### Claim 6 (depends on 2)

An isolated nucleic acid encoding a) the antibody or antigen binding fragment thereofof claim 2 or b) the VH or VL of the antibody or antigen binding fragment thereof.

### Claim 7 (depends on 5, 6)

An isolated expression vector comprising the isolated nucleic acid of claim 5 or 6.

### Claim 8 (depends on 5, 6)

A host cell comprising the isolated nucleic acid of claim 5 or 6.

### Claim 9 (depends on 8)

A method comprising culturing the host cell of claim 8 under conditions that allow production of the antibody or antigen binding fragment, or VH or VL of the antibody or antigen binding fragment, and purifying the antibody or antigen binding fragment, or VH or VL of the antibody or antigen binding fragment, from the host cell.

### Claim 10 (depends on 1)

A composition comprising the isolated antibody or antigen binding fragment thereof of claim 1 and an antibiotic agent.

### Claim 11 (depends on 1)

A method of reducing aggregation of two or more bacteria the method comprising contacting the two or more bacteria with an effective amount of the antibody or antigen binding fragment thereof of claim 1.

### Claim 12 (depends on 1)

A method of inhibiting interaction between two or more autotransporter molecules the method comprising contacting at least one of said two or more autotransporter molecules with the antibody or antigen binding fragment thereof of claim 1.

### Claim 13 (depends on 1)

A method of treating a bacterial infection in a subject, the method comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of claim 1.

### Claim 14 (depends on 1)

A method of treating a disease or disorder associated with a bacterial infection in a subject the method comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of claim 1.